Major Depressive Disorder
Transcranial Magnetic Stimulation: Theoretical Basis and Evidence
New treatments for depression are in high demand, and repetitive transcranial magnetic stimulation (rTMS) has received attention as a potentially efficacious, novel technique that might be optimized for the treatment of major depressive disorder (MDD). Here, Brent Forester, MD, Chief, Division of Geriatric Psychiatry at McLean Hospital, a Harvard Medical School Affiliate, discusses the theory behind rTMS and considers the preliminary evidence for its efficacy.
Chief, Division of Geriatric Psychiatry
“Such interventions with bilateral rTMS are generally more effective than sham in improving depressive symptoms, although the effect size has been described as modest.”
Repetitive TMS uses 1.0-2.5 Tesla, focused magnetic field pulses to induce electrical currents in neural tissue noninvasively, via an inductor coil placed against the scalp, which has been shown to impact brain activity according to the applied frequency. High-frequency rTMS (usually ≥10 Hz) induces an increase in activity, whereas low-frequency rTMS (usually ≤1 Hz) has the opposite effect.
According to the MDD prefrontal asymmetry theory, abnormal structural asymmetry of the dorsolateral prefrontal cortex (DLPFC) is associated with depression. The asymmetry may be characterized by left frontal hypoactivation and right frontal hyperactivation. Thus, in bilateral rTMS, high-frequency rTMS and low-frequency rTMS are applied, respectively, over the left and right DLPFC. Standard protocols deliver rTMS once daily, 5 days/week. Clinical trials have found maximal effects at 26 to 28 sessions.
Such interventions with bilateral rTMS are generally more effective than sham in improving depressive symptoms, although the effect size has been described as modest.
Several new forms of rTMS therapy have emerged, and a recent systematic review and network meta-analysis by Brunoni and colleagues explored the efficacy of these different rTMS modalities for MDD treatment, comparing the effects of 8 rTMS interventions and sham in MDD using data from 81 randomized clinical trials (4233 patients with depression). Response to rTMS was defined as 50% or greater improvement from baseline according to the study primary depression scale. Response and remission rates were obtained from each study based on the study primary outcome scale; if, however, the study did not specify the primary outcome scale, the rates would be obtained based on the Hamilton Depression Rating Scale, 17-items (HDRS-17). Remission was defined as 7 or less, 8 or less, or 10 or less on the HDRS-17, HDRS-21, or Montgomery-Åsberg Depression Rating Scale (MADRS), respectively.
Brunoni and colleagues found that priming low-frequency, bilateral, high-frequency, low-frequency, and theta-burst rTMS—but not novel (accelerated, synchronized, and deep rTMS) strategies—were more effective than sham in response rates. All interventions were at least as acceptable as sham. Nonetheless, the authors concluded that available evidence on interventions other than bilateral, high-frequency rTMS, and low-frequency rTMS was scarce, calling for new, high-quality randomized clinical trials to establish their efficacy with a higher degree of credibility.
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